TrkB-mediated activation of geranylgeranyltransferase I promotes dendritic morphogenesis.
Dendrite morphogenesis is regulated by neuronal activity or neurotrophins, which may function by activating intrinsic signaling proteins, including Rho family GTPases. Here we report that activity- and brain-derived neurotrophic factor (BDNF)-dependent dendritic morphogenesis requires activation of geranylgeranyltransferase I (GGT), a prenyltransferase that mediates lipid modification of Rho GTPases. Dendritic arborization in cultured hippocampal neurons was promoted by over-expression of GGT, and reduced by inhibition or down-regulation of GGT. Furthermore, GGT was activated by neuronal depolarization or BDNF, both of which promote dendritic arborization, in cultured hippocampal neurons. Moreover, exploration of a novel environment caused activation of GGT in the mice hippocampus, suggesting that neural activity activates GGT in vivo. Interestingly, GGT was physically associated with tropomyosin-related kinase B (TrkB), the receptor for BDNF, and this association was enhanced by depolarization. Disrupting the GGT-TrkB interaction or down-regulating GGT activity attenuated depolarization- or BDNF-induced dendrite development. Finally, the GGT effect on dendrite arborization was prevented by over-expressing Rac1 with the prenylation site deleted or mutated. Thus depolarization- or BDNF-dependent dendrite development may be mediated by GGT-induced prenylation of Rho GTPases.
Zhou
Xiu-Ping
XP
Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. zgluo@ion.ac.cn
Wu
Kong-Yan
KY
Liang
Bin
B
Fu
Xiu-Qing
XQ
Luo
Zhen-Ge
ZG
D019883:Alkyl and Aryl Transferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002478:Cells, Cultured; D003712:Dendrites / Q000201:enzymology* / Q000648:ultrastructure*; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D009024:Morphogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D054876:Prenylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism*; D014162:Transfection; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D020813:Receptor, trkB; D020830:rac1 GTP-Binding Protein